available online through - ijrap · international journal of research in ayurveda ... research...

Sahu Deepak et al / IJRAP 2011, 2 (2) 588-591

International Journal of Research in Ayurveda & Pharmacy, 2(2), 2011 588-591

Research Article Available online through www.ijrap.net ISSN 2229-3566

DEVELOPMENT OF ANALYTICAL METHOD FOR QUETIAPINE FUMARATE BY

UV SPECTROPHOTOMETRY Sahu Deepak1*, Rana A. C2

1Geetanjali Institute of Pharmacy, Airport road, Dabok, Udaipur, Rajasthan, India 2Rayat Institute of Pharmacy, Ropar Distt. Nawanshahr, Punjab, India

Received on: 14/01/2011 Revised on: 26/02/2011 Accepted on: 12/03/2011

ABSTRACT A Simple, sensitive, specific, Spectrophotometric method has been developed for the detection of quetiapine fumarate in pure form and in Pharmaceutical formulations. The optimum condition for the analysis of the drug was established. Quetiapine Fumarate exhibiting absorption at 242nm and obeyed beers law in the concentration range 5 to 25μg/ml. The lower limit of detection was found to be 3.5×10-2 and the limit of quantification to be 11.6 ×10-2. The regression equation was y = 0.037x + 0.007. The precision of the method was found to be 100.14 mg at 242 nm against the label claim of 100 mg. The sample solution was stable up to 24 hours. The assay results were found to be in good agreement with label claim. The proposed method was simple sensitive, precise, quick and useful for routine quality control. KEYWORDS: Spectrophotometry; Quetiapine Fumarate; Determination. *Corresponding Author Deepak Sahu, M.Pharm Student, Geetanjali Institute of Pharmacy, Dabok, Udaipur, Raj, India Email: [email protected] INTRODUCTION Quetiapine fumarate is the most recently introduced atypical antipsychotic and is indicated for the management of the manifestations of psychotic disorders and schizophrenia. Quetiapine, like clozapine (the archetypal atypical antipsychotic), interacts with a broad range of neurotransmitter receptors and has a higher affinity for serotonin (5-HT(2A)) receptors relative to dopamine (D(2)) receptors in the brain. Further, quetiapine's pharmacological effects appear selective for the mesolimbic and mesocortical dopamine systems, which are believed to be the areas of the brain responsible for the therapeutic effects of antipsychotics.1-

4. In contrast to most standard antipsychotics and some atypical antipsychotics, quetiapine's effects on the nigrostriatal dopamine system, which is responsible for the extrapyramidal (or motor) side effects, are minimal. Quetiapine also has minimal activity on dopamine receptors in the tubero infundibular dopamine system, thereby avoiding the problem of hyperprolactinemia, common with the standard antipsychotics and some atypical antipsychotics. Because of these properties,

quetiapine is an effective antipsychotic agent with a relatively benign side effect profile.5-9 Several large, placebo- and active-controlled, multicenter trials have shown quetiapine to be effective against both positive (e.g., hallucinations, delusions) and negative symptoms (e.g., emotional withdrawal, apathy) and to have benefits in reducing hostility, aggression and affective symptoms.10-13 Patients on long-term treatment report high compliance, good satisfaction, increased ability to function and improvements consistent with a better quality of life. Because of quetiapine's excellent tolerability profile, its use is particularly appropriate in patients especially sensitive to adverse effects, e.g., elderly patients with psychotic symptoms and other neurological disorders such as Parkinson's and Alzheimer's disease.13 However, no literature was found on quantitation of quetiapine fumarate in tablets. The aim of the present work is to find out a simple, specific, sensitive, spectrophotometer method developed for the detection of Quetiapine Fumarate in pure form and in pharmaceutical formulation.



MATERIAL AND METHOD Instrumentation A double–beam spectrophotometer shimadzu was used for the detection of absorbance, Mettler Toledo as Weighing balance and Misonix sonicator, borosil glass apparatus were used for experimental purpose. Chemicals and Reagents Quetiapine Fumarate working standard was supplied by M/S IPCA pharmaceutical Pvt. Ltd., Ratlam (M.P.). All other chemicals used in the analysis were AR grade. PROCEDURE Preparation of stock solution 100mg of mg pure drug was weighed and transferred to a 100ml volumetric flask, 50ml Phosphate Buffer pH 6.8 was added to the above flask, dissolved and sonicated for 15 min the volume was made up with the Phosphate Buffer pH 6.8. Preparation of sample solution The average weight of the tablets was determined by weighing 10 tablets and these were powdered. Tablet powder equivalent to 100 mg of quetiapine fumarate was weighed and transferred to a 100ml volumetric flask. About 20ml of phosphate buffer pH 6.8 was added and sonicated for 15min for complete dissolution of drugs the volume was made up with phosphate buffer pH 6.8 and filtered through filter paper. Six replicates of analysis were carried out with sample weighed individually. The average weight of tablet was found to be 419.829 mg. METHOD VALIDATION Validation of the analytical method14 for the determination of Quetiapine Fumarate in Pure form and in pharmaceutical formulation was carried out as per ICH guidelines. Linearity The method was validated according to ICH Q2B guidelines15 for validation of analytical procedures14,16-17 in order to determine the linearity, sensitivity, precision and of the analyse for quetiapine fumarate, five point calibration curves were generated with the appropriate volumes of the working standard solutions for UV methods. The linearity was evaluated by the least-square regression method using unweighted data. Precision Precision is the degree of repeatability of an analytical method under normal operational conditions. The precision and were determined with standard quality control samples (in addition to calibration standards) prepared in triplicate at different concentration levels covering the entire linearity range. The precision of the

assay was determined by repeatability (intra-day) and intermediate precision (inter-day) and reported as RSD % for a statistically significant number of replicate measurements. The intermediate precision was studied by comparing the assays on three different days and the results are documented as the standard deviation and RSD %. Accuracy15-16,18-19 is the percent of analyses recovered by assay from a known added amount. Data from nine determinations over three concentration levels covering the specified range were obtained. Limit of Detection and Limit of Quantification The limit of detection (LOD)16-17 is defined as the lowest concentration of an analyte that an analytical process can reliably differentiate from back-ground levels. In this study, LOD and LOQ were determined based on the standard deviation of the response and the slope of the corresponding curve using the following equations: LOD = 3.3 LOQ = 10 Where s, the noise of estimate, is the standard deviation of the absorbance of the sample and m is the slope of the related calibrations graphs. The limit of quantification (LOQ) is defined as the lowest concentration of the standard curve that can be measured with an acceptable accuracy, precision and variability. Stability The stability15,17,19-24 of quetiapine fumarate in phosphate buffer pH 6.8 solution was studied by the UV method. Sample solutions were prepared in triplicate and stored at 5°C and 27°C for 30, 60, 90, 120min and 24 hours. The stability of these solutions was studied by performing the experiment. RESULTS AND DISCUSSION Linearity studies were carried out in the concentration range of 5-25 µg/ml and the sample solution is obtained from the stock solution. The readings are obtained by measuring the absorbance at 242nm presented in table 1 and the curve was shown in fig.1. Performing replicate analyses of the standard solutions was used to assess the precision and reproducibility of the proposed methods. The selected concentration within the calibration range was prepared in phosphate buffer pH 6.8 and analyzed with the relevant calibration curves to determine the intra and inter day variability. The intra and inter day precision were determined as the RSD %. The precision, of the results are given in table 2, which demonstrate a good precision and the consolidated recovery data was presented in table 3.



The proposed methods can be successfully applied for quetiapine fumarate assay in tablet dosage forms without any interference. The assay showed the drug content of this product to be in accordance with the labelled claim 100mg. The values of LOD and LOQ are given in table 3. The stability25-26 of quetiapine fumarate in phosphate buffer pH 6.8 solution was studied by the UV method. Sample solutions were prepared in triplicate and stored at 5 and 27°C for 24hrs. The stability of these solutions was studied by performing the experiment. The stability of quetiapine fumarate in phosphate buffer pH 6.8 solution was evaluated to verify whether any spontaneous degradation occurs, when the samples were prepared. The stability profile for 24 hrs was studied. The results were expressed as a percentage of the drug remaining. The obtained data showed that the sample solutions were stable up to 24hrs. CONCLUSION The developed Spectrophotometric method was simple, sensitive, and specific, for the determination of quetiapine fumarate in pure and pharmaceutical formulations. The linearity of quetiapine fumarate, which obeys beer’s law, was 5-25μg/ml at 242nm and it shows regression more than 0.999. The precision of the method was found to be 100.02%. It could be precisely detected and quantified at 3.5×10-2 and 11.6 ×10-2 respectively. The sample solution was stable up to 24 hrs. The proposed method will be suitable for the analysis of quetiapine fumarate in pure and tablet dosage form. REFERENCES 1. Reynolds JEF, Eds., In; Martindale; The Extra Pharmacopoeia,

29th Edn, The Royal Pharmaceutical Society of Great Britain, London, 1993; 295.

2. McNaman JO, Hardman JG, Limbird LE, Molinoff PB and Ruddon RW. Eds., The Pharmacological Basis of Therapeutics: 9th Edn. Mc Graw-Hill, New York, 1996, p. 46.

3. Clark’s Analysis of Drugs and Poisons, London; Pharmaceutical Press. Electronic version, 2006: 221

4. Indian Pharmacopoeia Ministry of Health and Family Welfare. Delhi: Controller of publications 1996.

5. Basavaraj H, Bennikallu HM, Mruthyunjayaswamy J, Development and validation of spectrophotometric methods for determination of ceftazidime in pharmaceutical dosage forms, Acta Pharm. 2008; 58: 275–285.

6. Lalwani AN, Parikh JR, Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release, Acta Pharm. 2008; 58: 309–316.

7. Nagaraja P., Naik SD, Shrestha AK, Anantharaman SK, A sensitive spectrophotometric method for the determination of sulfonamides in pharmaceutical preparations, Acta Pharm. 2007; 57: 333–342.

8. Nafisur R., Nishat A., Kashif M., Hoda N., A sensitive kinetic spectrophotometric method for the determination of captopril in bulk and dosage forms, Acta Pharm. 2006; 56: 347–357.

9. Pirzada SS, Bhatia SC, Petty F, Potential benefits of quetiapine in the treatment of substance dependence disorders, J Psychiatry Neurosci 2004; 29(6): 452-457.

10. Stauffer V, Svanum HA, Liu L., Ball T and Conley R, Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind randomized clinical trials, BMC Psychiatry, 2009; 13.

11. Muller C, Reuter H, and Dohmen C, Intoxication after Extreme Oral Overdose of Quetiapine to Attempt Suicide: Pharmacological Concerns of Side Effects, Case Reports in Medicine, Hindawi Publishing Corporation, 2009; 5.

12. Geddes J, Freemantle N, Harrison P, Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis, BMJ Psychiatry, 2000; 321: 1371–1376.

13. Schwartz TL, Masand PS, Treatment of Delirium With Quetiapine, Primary Care Companion, J Clin Psychiatry, 2000; 10-12.

14. Blessborn AD, Bergqvist Y, Day N, White NJ, Development and validation of a bioanalytical method using automated solid-phase extraction and LC-UV for the simultaneous determination of lumefantrine and its desbutyl metabolite in plasma, In J Pharm Biomed Anal, 2005; 37 (5): 1081-1088.

15. International Conference of Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Validation of Analytical Procedures: Methodology, Adopted in Geneva, 1996.

16. Blessborn D, Romsing S, Annerberg A, Sundquist D, Bjorkman A, Lindegardh N, Bergqvist Y, Development and validation of an automated solid-phase extraction and liquid chromatographic method for determination of Lumefantrine in capillary blood on sampling paper, J Pharm Biomed Analys, 2007; 45(2): 282-287.

17. Hokanson GC., A Life Cycle Approach to the Validation of Analytical Methods during Pharmaceutical Product Development, Part – II: Changes and the Need for Additional Validation, Pharm. Tech., 1994; 92 -100.

18. Costa CI, Nogueira FH, Pianetti GA, Comparison of HPLC, UV spectrophotometry and potentiometric titration methods for the determination of lumefantrine in pharmaceutical products, J Pharm Biomed Anal, 2008; 48 (1): 223-236.

19. Vessman J., Selectivity or Specificity? Validation of Analytical Methods from the Perspective of an Analytical Chemist in the Pharmaceutical Industry, J. Pharm and Biomed. Anal., 1996; 14: 867 – 869.

20. Green JM., A Practical Guide to Analytical Method Validation, Anal. Chem. News and Features, 1996; 305A – 309A.

21. Lindegardh NW, Singh SP, Jain GK, Determination of Quetiapine Fumarate in rat plasma by liquid-liquid extraction using LC-MS/MS with electrospray ionization: assay development, validation and application to a pharmacokinetic study, J Chromatogr 2009; 877(11-12): 1133-1139.

22. Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP, In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether- Lumefantrine (Coartem). J Infect Dis., 2005; 191(6): 1014-1017.

23. Wahajuddin K, Singh SP, Jain GK, Determination of lumefantrine in rat plasma by liquid-liquid extraction using LC-MS/MS with electrospray ionization: assay development, validation and application to a pharmacokinetic study, J Chromatogr B, 2009; 877(11-12): 1133-1139.

24. Wegscheider P, Guenzler H., Validation of Analytical Methods, in: Accreditation and Quality Assurance in Analytical



Chemistry, Springer (Ed.) Verlag, Berlin. World Health Organization, W.H.O, 1996; 47.

25. Colussi D, Parisot C, Legay F, Lefevre G, Binding of artemether and Lumefantrine to plasma proteins and erythrocytes, Eur J Pharm Sci., 1999; 9: 9–16.

26. Fifield FW. and Kealey D, 5th Edition, Black Well Science Ltd. Principles and Practice of Analytical Chemistry, 2000; 270 – 276.

Table 1: Linearity profile of Quetiapine Fumarate

S. No Concentration (mmmmg/ml)

Absorbance at 242 nm

1 0 0.000 2 5 0.183 3 10 0.365 4 15 0.545 5 20 0.744 6 25 0.950

Correlation coefficient = 0.999 Absorbance = 0.037 × concentration - 0.007 Values in parenthesis indicates standard deviation (n = 3)

Table 2 Precision data for Quetiapine Fumarate in formulation

S. No. Weight (mg)

Absorbance (Ao)

Amount (mg)

1 419.82 0.379 99.89 2 420.13 0.386 100.23 3 419.84 0.376 99.94 4 419.98 0.384 100.11 5 420.27 0.387 100.45 6 419.80 0.382 99.85

Average

100.078

SD

0.231

Table 3: Validation parameter of Quetiapine Fuamrate S. No. Parameters Quetiapine

Fumarate 1 Measured Wavelength

(λmax) 242

2 Linearity Range (mg/ml) 5-25 3 Slope 0.037 4 Intercept 0.007 5 Percentage Recovery 99.92 6 Correlation Coefficient (r) 0.999 7 Limit of Detection (LOD),

(mg/ml) 0.0237

8 Limit of Quantification (LOQ), (mg/ml)

0.123

Figure 1: Linearity curve of Quetiapine Fumarate

Source of support: Nil, Conflict of interest: None Declared

available online through - ijrap · international journal of research in ayurveda ... research...

Documents